PSMA-PET/MRI-Based Focal Dose Escalation in Patients with Primary Prostate Cancer Treated with Stereotactic Body Radiation Therapy (HypoFocal-SBRT)

Study PIs:

Prof. Dr. Anca-L. Grosu (Freiburg)
PD Dr. Constantinos Zamboglou (Freiburg)
Dr. med. Simon Spohn (Freiburg)
Prof. Dimos Baltas (Freiburg)


● Recruiting centers

Study design:
● Multi-center, international, randomized, prospective, interventional 2-arm phase II study

Inclusion Criteria:
Histologically confirmed adenocarcinoma of the prostate (histological confirmation can be based on tissue taken at any time, but a re-biopsy should be considered if the biopsy is more than 12 months old)
Primary localized PCa (cN0 and cM0 in mpMRI and PSMA-PET): high- or very high-risk according to NCCN v2.2021 OR unfavorable intermediate-risk disease according to NCCN v2.2021
● Signed written informed consent for this study
● Age > 18 years
● Previously conducted PSMA-PET/CT and mpMRI scans or PSMA-PET/MR for staging, fulfilling standard requirements for PCa
● ECOG performance score 0 or 1
● IPSS score ≤ 15
● Prostate volume ≤ 75 mL at RT planning

Exclusion criteria:
● Evidence of neuroendocrine tumor cells
● Prior radiotherapy to the prostate or pelvis
● Prior radical prostatectomy
● Prior focal therapy approaches to the prostate
● Time gap between the beginning of ADT and conduction of initial mpMRI and PSMA-PET scans is >1 month
● Radiologically suspicious or pathologically confirmed lymph node involvement (cN+) in mpMRI and/or PSMA-PET/CT
● Evidence of metastatic disease (cM+) in mpMRI and/or PSMA-PET/CT
● Evidence of cT4 disease in mpMRI and/or PSMA-PET/CT
● PSA > 30 ng/mL prior to starting ADT
● Expected patient survival <5 years
● Bilateral hip prostheses or any other implants/hardware that would introduce substantial CT artefacts
● Contraindication to undergo a mpMRI scan
● Prostate surgery (TURP or HOLEP) with a significant tissue cavity or prostate surgery (TURP or HOLEP) within the last 6 months prior to randomization
● Medical conditions likely to make radiotherapy inadvisable, e.g., acute inflammatory bowel disease, hemiplegia or paraplegia
● Previous malignancy within the last 2 years (except basal cell carcinoma or squamous cell carcinoma of the skin), or if previous malignancy is expected to significantly compromise 5 year survival
● Any other contraindication to external beam radiotherapy (EBRT) to the pelvis
● In mpMRI and PSMA-PET/CT or PSMA-PET/MRI scans, no visible tumor
● Participation in any other interventional clinical trial within the last 30 days before the start of this trial
● Simultaneous participation in other interventional trials that could interfere with this trial; simultaneous participation in registry and diagnostic trials is allowed
● Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial
● Known or persistent abuse of medication, drugs or alcohol
● Patients expected to have severe set up problems
● Dose constraints for organs at risk cannot be adhered to

Sample size:
● 374 patients with unfavorable intermediate- / High-Risk prostate cancer staged cN0 und cM0 in PSMA-PET/CT and MRI recruiting at 22 centers in Germany, Switzerland, Austria and Cyprus

● Primary endpoint: relapse free survival (RFS)
● Secondary endpoint: time to local failure, metastatic free survival, overall (OS), prostate cancer specific survival (PCSS) and time to biochemical failure
● additional research: patient-reported outcomes, feasibility and adherence to dose constraints

Trial Registration